Development of a degrader against oncogenic fusion protein FGFR3-TACC3 was written by Shibata, Norihito;Cho, Nobuo;Koyama, Hiroo;Naito, Mikihiko. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2022.Electric Literature of C3H9NO The following contents are mentioned in the article:
Fibroblast growth factor receptor 3-transforming acidic coiled-coil containing protein 3 (FGFR3-TACC3), which has been identified in many cancers such as glioblastoma and bladder cancer, is a potent oncogenic fusion protein that induces constitutive activation of FGFR signaling, resulting in uncontrolled cell proliferation. Although several tyrosine kinase inhibitors against FGFR are currently under development, resistance to such types of inhibitors in patients has become a concern. In this study, a chimeric mol. SNIPER(TACC3)-11 I was developed and found to reduce FGFR3-TACC3 levels effectively. Compound I conjugated KHS108 (a TACC3 ligand) to an LCL161 derivative II (an inhibitor of apoptosis protein [IAP] ligand) with a PEG linker (n = 2). Mechanistical anal. showed that cellular IAP1 was required for the reduction of FGFR3-TACC3 levels. Consistent with the decrease in FGFR3-TACC3 levels, compound I suppressed the growth of FGFR3-TACC3 pos. cells. Thus, compound I is a candidate therapeutic with a novel drug modality against cancers that exhibit FGFR3-TACC3-dependent proliferation and exerts pharmacol. effects distinct from FGFR3 kinase inhibitors because it lacks substructures crucial for kinase inhibition. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3Electric Literature of C3H9NO).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials.Electric Literature of C3H9NO
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem